A role of valency of concanavalin A and its chemically modified derivatives in lymphocyte activation. Monovalent monomeric concanavalin A derivative can stimulate lymphocyte blastoid transformation.

A concanavalin A (ConA) derivative of a monovalent monomeric nature, including a monomeric molecular weight at pH 7.4, significantly induces lymphocyte blastoid transformation. The derivative was recently obtained by Tanaka, I., Abe, Y., Hamada, T., Yonemitsu, O., and Ishii, S. ((1981) J. Biochem. (Tokyo) 89, 1643-1646) by a novel procedure of photochemically induced alkylation of tryptophan residues of native tetravalent ConA using a high pressure mercury lamp in the presence of chloroacetamide followed by two steps of column chromatography. This monovalent monomeric ConA (Mm-ConA) was demonstrated to be almost equally potent in producing the maximal response of lymphocytes when compared with native tetrameric ConA, although Mm-ConA was required at about 70 times as high as the concentration of native ConA on a weight basis to attain the maximal response of lymphocyte activation. The binding potency of the former to lymphocytes was about two-thirds as potent as that of the latter. Mm-ConA failed to agglutinate sheep erythrocytes at concentrations 1800-fold higher than native tetravalent ConA, but showed a weak but definite agglutinating activity against guinea pig erythrocytes at a relatively high concentration (approximately 80 micrograms/ml). Cell cluster formation was observed in lymphocyte cultures for 24 to 48 h with Mm-ConA where DNA replication in stimulated lymphocytes was observable. No significant difference was observed between sizes of cell clusters formed in the presence of Mm-ConA and of native tetravalent ConA at this phase of lymphocyte activation. The present results suggest that the multivalency of ConA with respect to sugar-binding sites may not be a stringent requirement for lymphocyte activation, and that another binding site for cell membrane, which has been suggested to exist in the ConA protomer and to be hydrophobic (membranophilic), may play a subsidiary but important role in triggering lymphocyte blastoid transformation as well as hemagglutination with Mm-ConA. The biological significance in lymphocyte activation of lectin valency with respect to sugar-binding sites has been discussed, comparing the effects of various ConA derivatives of different valencies, including a monovalent monomer (Mm-ConA), divalent dimers (beta-ConA, sulfomethylamino-ConA, and succinylated ConA), and tetravalent tetramers (alpha-ConA), on the cell surface.